Endophytes, microorganisms that reside in the tissues of living plants, are relatively unstudied and potential sources of novel natural products for exploitation in medicine, agriculture and industry. It is worthy to note, that of the nearly 300,000 plant species that exist on the earth, each individual plant is host to one or more endophytes. Only a handful of these plants have ever been completely studied relative to their endophytic biology. Consequently, the opportunity is great to find new and interesting endophytic microorganisms among myriads of plants in different settings, and ecosystems.
Currently, endophytes are viewed as an outstanding source of bioactive natural products because there are so many of them occupying literally millions of unique biological niches (higher plants) growing in so many unusual environments. While the symptomless nature of the occupation of plant tissues by endophytes has prompted focus on symbiotic or mutualistic relationships between endophytes and their hosts, the observed biodiversity of endophytes suggests they can also be aggressive saprophytes or opportunistic pathogens. Both fungi and bacteria are the most common microbes existing as endophytes (Bacon and White, Microbial Endophytes. Marcel Dekker Inc., N.Y., 2000). For example, some of these organisms make compounds now exploitable as anticancer drugs, antibiotics, and antioxidants.
There is a need for more and better antimycotics, as the human population is developing more fungal infections. This is particularly an issue with immunosuppressed patients, such as HIV/AIDS patients, patients with organ-transplants, and anyone who must take immunosuppressive drugs. In both cases, patients with these difficulties have immune systems that are weakened. Antifungal agents that are currently available, such as cyclosporin A, are toxic to the subject, and often ineffective against the fungal pathogen.
Since the discovery of cyclosporin A from Trichoderma polysporum in 1976, it has been the principal immunosuppressive agent used in medicine (Ruegger et al., Hel. Chim. Acta. 59: 1075-1092, 1976). Presently, cyclosporin A, along with tacrolimus (FK506) and sirolimus (rapamycin) are three immunosuppressants which act on CD4+ T cells used in clinical practice. These compounds have gained wide spread acceptance for use in organ and tissue transplantation, various autoimmune diseases and with some other non-autoimmune inflammatory diseases. However, all three drugs can cause nephrotoxicity (Daoud et al., Epilepsia 48: 834-836, 2007). In addition, cyclosporin A and tacrolimus can cause neurotoxicity and beta-cell toxicity (Tanabe, Drugs 63: 1535-48, 2003; Froud et al., Cell Transplant 15: 613-620, 2006). Cyclosporin A can cause more serious nephrotoxicity, hypertension and hyperlipidaemia in comparison to tacrolimus (Andoh et al., Kidney Int. 50: 1110-1117, 1996). Novel compounds with low toxicity that act in an effective and useful manner will contribute to the arsenal of substances that act to suppress the immune system and will be especially helpful to those with autoimmune diseases and organ recipients.
There is also a need for environmentally sound ways to control pests and pathogens (Overton, Ecologically Based Pest Management—New Solutions for a New Century. Natl. Aca. Press. Washington D.C., 1996). In the past, the major source of pesticidal agents came from organic synthesis. Recently, interest has increased for using more environmentally friendly methods in agricultural production, including naturally-occurring biological compounds.